Background: Serious illness often causes economic hardship for patients' families. However, it is not known whether this hardship is associated with a preference for the goal of care to focus on maximizing comfort instead of maximizing life expectancy or whether economic hardship might give rise to disagreement between patients and surrogates over the goal of care. Methods: We performed a cross-sectional study of 3158 seriously ill patients (median age, 63 years; 44% women) at 5 tertiary medical centers with 1 of 9 diagnoses associated with a high risk of mortality. Two months after their index hospitalization, patients and surrogates were surveyed about patients' preferences for the primary goal of care: either care focused on extending life or care focused on maximizing comfort. Patients and surrogates were also surveyed about the financial impact of the illness on the patient's family. Results: A report of economic hardship on the family as a result of the illness was associated with a preference for comfort care over life-extending care (odds ratio, 1.26; 95% confidence interval, 1.07-1.48) in an age-stratified bivariate analysis. Similarly, in a multivariable analysis controlling for patient demographics, illness severity, functional dependency, depression, anxiety, and pain, economic hardship on the family remained associated with a preference for comfort care over life-extending care (odds ratio, 1.31; 95% confidence interval, 1.10-1.57). Economic hardship on the family did not affect either the frequency or direction of patient-surrogate disagreements about the goal of care. Conclusions: In patients with serious illness, economic hardship on the family is associated with preferences for comfort care over life- extending care. However, economic hardship on the family does not appear to be a factor in patient-surrogate disagreements about the goal of care.